Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis

Summary This is a phase Ib/II study of regorafenib plus toripalimab for colorectal cancer. The objective response rate (ORR) is 15.2% and the disease control rate is 36.4% in evaluable patients with recommended phase II dose (80 mg regorafenib plus toripalimab). The median progression-free survival (PFS) and the median overall survival are 2.1 months and 15.5 months, respectively. Patients with liver metastases have lower ORR than those without (8.7% versus 30.0%). All patients (3/3) with lung-only metastasis respond, whereas no patients (0/4) with liver-only metastasis respond. 94.9% and 38.5% of patients have grade 1 and grade 3 treatment-related adverse events, respectively. Gut microbiome analysis of the baseline fecal samples shows significantly increased relative abundance and positive detection rate of Fusobacterium in non-responders than responders. Patients with high-abundance Fusobacterium have shorter PFS than those with low abundance (median PFS = 2.0 versus 5.2 months; p = 0.002).
Graphical abstract
Highlights Regorafenib plus toripalimab improves response and overall survival Patients with liver metastasis have lower response rate than those without Increased Fusobacterium is found in non-responders compared with responders
Wang et al. demonstrate the safety, efficacy, and survival of regorafenib plus toripalimab in colorectal cancer patients. They show the gut microbiome results that Fusobacterium is negatively correlated with response and survival. This provides a combination regimen for unselected refractory metastatic colorectal cancer patients.